Agonism Of Gpr40 Protects The Capacities Of Epidermal Stem Cells (Escs) Against Ultraviolet-B (Uv-B)

Introduction: Skin damage due to overexposure to ultraviolet B (UV-B) radiation can lead to the development of cancers and reduce the skin's functionality as a vital protective barrier. Epidermal stem cells (ESCs) are pluripotent cells responsible for skin regeneration and healing. Upon exposure to UV-B radiation, ESCs produce excess amounts of reactive oxygen species (ROS) and inflammatory cytokines. However, the functional protection of ESCs is not fully explored. G-protein coupled G protein-coupled receptor 40 (Gpr40) is a free fatty acid receptor that is emerging as a potential treatment target for various diseases. Gpr40 has been found to be expressed in various cell types.Methods: ESCs were exposed to UV-B at the intensities of 25, 50, and 100 mJ/cm(2) for 24 h using TL 20 W/12 RS UV lamps. ESCs were treated with UV-B at 50 mJ/cm(2) in the presence or absence of 25 or 50 mu M of the Gpr40 agonist GW9508 for 24 h. The gene expression of the Wnt1 pathway and proinflammatory cytokines were evaluated. To antagonize Gpr40 expression, ESCs were treated with 10 mu M GW1100.Results: Our findings demonstrate that Gpr40 agonism can reduce the production of ROS as well as the expression of interleukins 1 beta and 8, two key proinflammatory cytokines. We demonstrate that agonism of Gpr40 can rescue the reduction in integrin beta 1 and Krt19 induced by UV-B exposure, thereby improving the capacities of ESCs to resist UV-B damage. Moreover, we show that the effects of Gpr40 agonism observed in our experiments are mediated through the Wnt/beta-catenin canonical signaling pathway, as evidenced by the expression of Wnt1 and cyclin D1.Conclusion: Our findings present evidence of the role of Gpr40 agonism in mediating the protective capacities of ESCs against insult from UV-B radiation.